The present proposal seeks electrophysiologic correlates to the well-known anatomic, biochemical, and mnemonic deficits of Alzheimer's Disease (AD). Aged nonhuman primates exhibit many similar deficits, including plaques, tangles, loss of neurons, neurotransmitter alterations, and memory disturbances. Thus, aged monkeys are presently the best model for single unit electrophysiologic studies relevant to AD. Because the primary function of the brain is to process information by means of its electrical activity, electrophysiologic correlates are necessary to evaluate the significance of molecular and anatomic changes in AD: any such alterations that do not result in electrophysiologic disturbances are unlikely to have much etiologic significance. Moreover, electrophysiologic deficits could themselves be important causes of AD cognitive impairment. The proposed experiments will employ four 5-7-year-old and four 28-32-year-old C. apella monkeys. These animals are being provided by Lederle Laboratories, and the present research will be one facet of comprehensive behavioral, electrophysiologic, and anatomic studies by the Lederle scientists and their collaborators (e.g., the PI) at other institutions. The specific aims of the present research are to test locus coeruleus (LC), nucleus basalis of Meynert (nBM), and cortical neuron spontaneous discharge characteristics, axonal conduction velocities, refractory periods, and cortical responsiveness to LC and nBM stimulation. There are precedents from the PI's previous research in cerebellum for changes at all these levels, any one of which could profoundly alter cortical information processing and cognitive function. The proposed project meets multiple criteria for the NIA small grant program: 1) The PI is recently trained, and is setting up his first laboratory. 2) The PI is moving into a research area, primate cortical electrophysiology, that is both new for him and more relevant to AD (preliminary data in rats and one young monkey are shown, however, to demonstrate that the PI has the necessary technical competence to carry out the research). 3) The research is innovative, in that there are only a handful of previous electrophysiologic studies of aging and dementia--none in primates. 4) The proposed experiments would provide a basis for more extended research.